An increased spontaneous and stimulated growth hormone (GH) secretion is well documented in insulin-dependent diabetes mellitus. On the contrary, in non-insulin-dependent diabetes mellitus (NIDDM) conflicting results arise from literature. In 14 patients with NIDDM, 7 normal weight (NWD) and 7 obese (OD), we investigated the somatotrope responsiveness to GHRH (1 microgram/kg) alone or combined with arginine (ARG, 0.5 g/kg), which is able to enhance the GH response to GHRH, probably by inhibiting somatostatin release from hypothalamus. Baseline IGF-I, IRI FFA and glucose levels were also determined. Twelve healthy normal subjects (NS) and 12 obese patients (OP) were evaluated as control groups. GH but not IGF-I levels were higher (p < 0.05) in NS than in OP (1.5 +/- 0.5 vs 0.5 +/- 0.2 microgram/l). Insulin levels were higher (p < 0.05) in OP than in NS, NWD and OD (18.7 +/- 1.8 vs 8.7 +/- 0.5, 6.4 +/- 1.9 and 11.8 +/- 1.2 microU/l). FFA were higher (p < 0.05) in NWD. OD and OP than in NS (0.69 +/- 0.04, 0.70 +/- 0.04 and 0.65 +/- 0.06 vs 0.39 +/- 0.03 mmol/l). Plasma glucose was higher (p < 0.05) in diabetic patients than in normal and obese subjects. GH responses to GHRH in NWD, OD and OP were similar (AUC: 221.6 +/- 33.3, 206.0 +/- 35.9 and 177.2 +/- 57.3 micrograms/l/min, respectively) and all lower (p < 0.05) than that in NS (776.7 +/- 206.5 micrograms/l/min). ARG determined a significant increase of GHRH-induced GH release in all groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)